The peritoneal cavity of females is continuously subjected to irritation as determined by the composition of macrophages isolated from the fluid. Commonly 15% to 35% of the macrophages are peroxidase positive and of the same size as monocytes. The remaining macrophages are of increasing size accompanied by increasing content of hydrolytic and proteolytic enzymes. This apparent continuum of macrophage developmental stages provides a relevant example of human monocyte to macrophage development and, thus, the opportunity to investigate the functional activity of macrophages in various stages of maturation. Parallel studies with peritoneal macrophages and blood monocytes maturing to macrophages in vitro will enable us to assess the validity of the latter macrophages as a model for macrophage differentiation in vivo. The aim of this research is to characterize the differentiation and some functional activities of human macrophages under the influence of various biological response modifiers. This will give us a better understanding of how various signals influence macrophages to alter or destroy neoplastic cell growth. Specific aims for the coming year include: (1)\Continue the characterization of human peritoneal macrophages in comparison with blood monocytes maturing in the presence or absence of various stimuli. An emphasis will be put on the identification of factors (prostaglandins, LAF, interferon) secreted by these cells. (2)\Characterize, using column chromatography, the factor(s) in the peritoneal fluid which, in preliminary experiments, have been shown to inhibit monocyte to macrophage development. (3)\Continue to accumulate data on inhibitory and stimulatory effects on tumor cell growth and viability by characterized macrophage subpopulations.